1. How can the disease described above create a mismatch between ventilation and perfusion? Use your understanding of alveolar dead space and physiologic shunt to explain your answer.
In coal-miner’s pneumoconiosis, respirable coal dust that are inhaled for long periods of time trigger hyperactive immune responses that lead to destruction of the lung. At the beginning, coal dust particles are expelled out of the lung through the function of pulmonary macrophages beneath the epithelial layer of airways and near capillaries (Kopf, Schneider & Nobs, 2015). These macrophages phagocytize the dust particles and transport them to the lymphatic tree or the larger airways for mucociliary clearance (Kopf, Schneider & Nobs, 2015). This mechanism functions protectively to rid the lungs of harmful irritants.
Over time and if large amounts of coal dust are inhaled, the mechanism for clearance becomes dysfunctional. Macrophages with phagocytized dust accumulate in the interstitium surrounding the bronchioles and capillaries stimulating fibroblasts to produce reticulin – a type of collagen fiber (Karkhanis & Joshi, 2013). Fibrosis occurs as reticulin is deposited around the macrophages forming macules that trap the dust-containing cells. The macrophages lyse when they reach the end of their lifespan releasing the coal dust they contain (Badawy, Quarn & Mohamadeen, 2013). Other macrophages are attracted to the area and re-phagocytize the dust leading to progressive thickening. Fibrosis causes the tissues surrounding the bronchioles to harden which distends the bronchioles permanently and at the terminal bronchioles also lead to alveoli that are similarly dilated, a condition referred to as emphysema (Badawy, Quarn & Mohamadeen, 2013). The destruction of the alveoli reduces the surface area available for the exchange of gases. Meanwhile, fibrosis around macrophages in the lymphatic tree causes ischemia as adjacent pulmonary capillaries are compressed.
Ventilation-perfusion mismatch occurs when there is inequality in the ratio of the amount of oxygen inhaled and the amount of blood that circulates to the lungs (Mattson Porth, 2011). In coal-miner’s pneumoconiosis, areas of ischemia of the pulmonary capillaries but with still functioning alveoli create alveolar dead space. The oxygen level is high here but the carbon dioxide level is low. This is because very little blood passes through the area and the diffusion of oxygen from the alveoli into the blood as well as the diffusion of carbon dioxide from the blood to the alveoli is low (Mattson Porth, 2011). High ventilation but low perfusion leads to an increased ratio of these two values.
Meanwhile, areas of emphysema but with good perfusion result in physiological shunting. It is the process wherein the normal amount of blood circulates to the lung but without functioning alveoli, no oxygen can diffuse to the blood. As such, the oxygen and carbon dioxide levels of blood that passes through these hypoxic areas approach those of venous blood (Mattson Porth, 2011). Low ventilation with high perfusion results in a low ratio of the two.
2. Individuals with chronic obstructive pulmonary disease have more difficulty exhaling than inhaling. Why is this so?
Chronic obstructive pulmonary disease (COPD) is of two types – emphysema and chronic bronchitis. In a normal airway, the rate of airflow into and out of the lungs is influenced partly by airway resistance – the quality of airways wherein they easily expand and return to their usual diameter influencing the pressure within the lungs (Lee, Taneja & Vassallo, 2012). During inhalation, the bronchioles expand and the increased volume reduces pressure permitting air from the atmosphere to enter the lungs. Conversely, during exhalation, the bronchioles return to their normal size and the narrowing reduces the volume. This increases the pressure and allows carbon dioxide to exit the lungs.
Emphysema in coal-miner’s pneumoconiosis is characterized by permanently dilated bronchioles indicating low airway resistance. The small airways do not pose as much of a problem in moving in air during inhalation because of the fact that they are already dilated. However, as they cannot return to their original size to cause the necessary changes to volume and pressure, it is more difficult to move air out of the lungs.
3. In general terms, what mechanisms in lung disease can affect diffusing capacity across alveolar membranes? Use the Fick law to explain your answer.
The Fick Law states that the volume (V) of oxygen or carbon dioxide diffusing through the alveolar-capillary membrane per minute (T), and per 1 millimeter hydrogen as the pressure gradient, depends on several factors. These are the differences in gas pressure (P1 - P2) between the two sides of the membrane, the diffusion coefficient (D) of the specific gas, and the membrane’s surface area (SA) (Mattson Porth, 2011). Diffusion coefficient is influenced by gas characteristics, one example of which is molecular weight, and is a constant value for each gas. Volume is also inversely proportional to the thickness of the membrane (Mattson Porth, 2011). Diffusing capacity (DL) for oxygen (O2) is derived from the Fick Law. The formula is DL = O2 consumption per minute / pAO2 – pO2 where pAO2 refers to alveolar oxygen and pO2 to capillary oxygen (Mattson Porth, 2011). The O2 consumption pertains to volume or the amount of O2 contained in blood per minute.
In lung diseases such as coal-miner’s pneumoconiosis, the surface area of the alveolar membrane is markedly reduced because of the dysfunctional alveoli. In addition, there are areas of the lungs with inadequate perfusion because of the compression of capillaries by reticulin deposition. Given the formula, a lower alveolar-capillary membrane surface area affects oxygen consumption per minute, pAO2, and pO2 and reduces diffusing capacity. The mechanism is different in pneumonia wherein fluids accumulate in the alveoli and increase the distance that oxygen has to move through in order to diffuse into the blood. This also reduces the diffusing capacity. In cystic fibrosis, viscous mucus clogs the airways leading to lower oxygen consumption and diffusing capacity as well.
References
Badawy, M.S., Qarn, A.F.E, & Mohamadeen (2013). Clinical features of alpha 1 antitrypsin deficiency in COPD. Egyptian Journal of Chest Diseases and Tuberculosis, 62(1), 71-77. doi:10.1016/j.ejcdt.2013.05.007
Karkhanis, V.S., & Joshi, J.M. (2013). Pneumoconioses. Indian Journal of Chest Disorders and Allied Sciences, 55, 25-34. Retrieved from http://www.medind.nic.in/iae/t13/i1/iaet13i1c.shtml
Kopf, M., Schneider, C., & Nobs, S.P. (2015). The development of function of lung-resident macrophages and dendritic cells. Nature Immunology, 16, 36-44. doi:10.1038/ni.3052
Lee, J., Taneja, V., & Vassallo, R. (2012). Cigarette smoking and inflammation: Cellular and molecular mechanisms. Journal of Dental Research, 91(2), 142-149. doi: 10.1177/0022034511421200.
Mattson Porth, C. (2011). Essentials of pathophysiology: Concepts of altered health states (3rd ed.). Philadelphia, PA: Wolters Kluwer Health.
